The objective of this research project is to ascertain the capacity for repair of specific types of carcinogen-induced DNA-based damage in the nuclei of hepatocyte and non-hepatocyte cell populations of precancerous rat liver. This may lead to an identification of those situations in which the possibility of aberrant gene expression becomes increasingly likely. Precancerous liver will be obtained by maintaining rats on diets containing either 2-acetylaminofluorene or 4-dimethylaminoazobenzene. The effect of the duration of carcinogen ingestion on the degree of covalent binding to, and the rate and extent of removal of carcinogen from, the DNA of the two hepatic cell populations will be determined. DNA extracted from the nuclei fractions of precancerous liver will be enzymatically digested to nucleosides which will be separated, by employing high pressure liquid chromatography, to discern specific reaction products of the carcinogen with DNA bases. An attempt will be made to determine whether the capacity to repair specific types of hepatic DNA-base damage is altered during the continued feeding of hepatic carcinogens. The capacity of DNA from precancerous liver to serve as a template for RNA synthesis will be measured and used as a functional measure of DNA repair. The activities of several enzymes involved in the DNA repair process, and the degree of single strand interruptions in DNA, will be determined in precancerous liver as a function of time on a carcinogenic diet. Novikoff hepatoma cells grown in suspension culture will be employed for studies on the fidelity of the DNA repair process, as assessed by changes in mutation frequency.